This project is to study the mechanisms of measles virus-induced suppression of the immune response of human peripheral blood lymphocytes, because this function has been found to be defective in patients with multiple sclerosis. The principal effector in this system has been found to be an non-T, non-B, non-adherent null lymphocyte, and the suppression appears to be mediated by interferons. Another null lymphocyte which is also regulated by interferon, the natural killer cell, also exhibits significantly decreased activity in patients with multiple sclerosis. The underlying basis of the observed defects in measles-induced suppression, interferon production, and natural killer cell activity are currently under investigation. We are developing and modifying new techniques in order to purify and identify the individual effector cells of each of these functions. In so doing, it is hoped to determine whether the decreased activities seen in peripheral blood lymphocytes of multiple sclerosis patients result from an absence of the appropriate effector cells from the circulation, or to abnormalities in their morphology or function.